8) Infectious Disease (Part 2) Flashcards
TB transmission
- Person to person by droplet nuclei
- Aerosolized by coughing, sneezing or speaking
TB infectivity correlates
- Concentration of organisms in expectorated sputum
- Extent of pulmonary disease
- Frequency of cough
- Intimacy & duration of contact
Pathophysiology of TB
- Aerosolized droplets enter lungs
- Tubercle Bacilli reach the alveoli and are ingested by alveolar macrophages
- In most individuals, M. tuberculosis infection is contained initially by host defenses, and infection remains latent
- Infection occurs if the inoculum escapes alveolar macrophage microbicidal activity
Latent TB infection
- T cells and macrophages surround the organisms in granulomas that limit their multiplication and spread
- These people do not have active disease and cannot spread the disease to others
- Clinically asymptomatic
- CXR is negative
- The only evidence of infection may be a reaction to the tuberculin skin test or positive interferon gamma release assay (IGRA)
Increased risk populations for TB
- Contacts of persons to have suspected or confirmed TB
- IV drug users
- Foreign born persons who recently arrived from a country with high TB incidence
- Health care workers who serve high-risk patients
- Residents and employees of high risk settings (correctional institutions, nursing homes, mental institutions, homeless shelters)
- Children and adolescents exposed to adults in high-risk categories
- Medical risk factors that increase the risk for TB (i.e. silicosis, HIV infection, CKD, leukemia, lymphoma, DM, unintentional weight loss, patients receiving immunosuppressive therapy etc.)
- Mycobacteriology laboratory personnel
Screening for latent TB
- Tuberculin skin test (TST) Or the interferon gamma release assay (IGRA)
Reading the Tuberculin Skin Test (Mantoux test of purified protein derivative/PPD)
- Measure reaction in 48 to 72 hours
- Measure induration (not erythema)
- Record reaction in millimeters, not “negative” or “positive”
Tuberculin skin test false positives
- Previous BCG vaccination
- Infection with nontuberculosis mycobacteria
- Incorrect method of TST administration
- Incorrect interpretation of reaction
- Incorrect bottle of antigen used
Tuberculin skin test false negatives
- Cutaneous anergy (anergy is the inability to react to skin tests because of a weakened immune system…such as HIV/AIDS)
- Recent TB infection (within 8-10 weeks of exposure)
- Very old TB infection (many years)
- Very young age (less than 6 months old)
- Recent live-virus vaccination (e.g., measles and smallpox)
Overwhelming TB disease - Some viral illnesses (e.g., measles and chicken pox)
- Incorrect method of TST administration
- Incorrect interpretation of reaction
interferon-gamma release assay (IGRA) tests for TB infection
- Blood Tests (must be processed within 8-16 hours after collection)
- Only one visit to health care provider to draw the blood
- Results can be available in 24 hours
- Results are not affected by prior (bacille Calmette-Guérin) BCG vaccination
Blood tests for TB
- Must be processed within 8-16 hours after collection
- QuantiFERON®-TB Gold test (QFT-G)
- QuantiFERON®-TB Gold In-Tube test (GFT-GIT)
- T-SPOT®- TB
Latent TB infection test results
- Positive Tuberculin skin test OR Positive QFT blood test
- Negative chest radiograph
- No symptoms or physical
findings suggestive of TB
disease
Pulmonary TB disease test results
- Tuberculin skin test or QFT (QuantiFERON-TB/QuantiFERON-Gold) blood test positive
- Chest radiograph may be abnormal
- Symptoms may include one or more of the following: fever, cough, night sweats, weight loss, fatigue, hemoptysis, decreased appetite
- Respiratory specimens may be smear or culture positive
Why treat latent TB?
- Reactivation possible
- Active Pulmonary TB Disease may occur in 10% of persons with Latent TB Infection
- Up to 50% of persons with HIV will develop Active Pulmonary TB Disease within 2 years of infection
Other conditions associated with increased incidence of developing Active Pulmonary TB Disease
- Silicosis
- DM
- Patient taking immunosupressive medications
Tx option for latent infection (negative CXR and no symptoms)
- Once weekly Isoniazide (INH) + Rifapentine x 3 months
- Daily Rifampin x 4 months
- Daily INH + Rifampin x 3 months
- INH x 6-9 months
- Supplement pyridoxine (vitamin B6) if prescribing INH to avoid peripheral neuropathy side effects
Active Pulmonary TB Disease
- 90% of the time, in adults, represents activation of latent disease
- Slow Progression of Constitutional Symptoms
Constitutional symptoms (slow progression) of active pulmonary TB disease
- Fever
- Loss of Appetite
- Weight Loss
- Night Sweats
- Fatigue
- Cough
- Blood-streaked sputum
CXR pulmonary TB
- Apical localization is characteristic
- This localization has been attributed to hyperoxic environment of apices
- Upper lobe disease marked by irregular reticular & nodular densities
Work-up and diagnosis of TB
- Respiratory isolation for all patients suspected of having Active TB
- Sputum cultures x 3 for Acid Fast Bacilli (stained smear + AFB confirmed with identification of M. tuberculosis in cultures).
- Xpert MTB/RIF, a rapid molecular test that accurately diagnoses TB and MDR-TB in 100 minutes
Sputum cultures x 3 for Acid Fast Bacilli in TB patients
- Stained smear + AFB confirmed with identification of M. tuberculosis in cultures
- Sample must be brought up from a productive cough
Induced sputum production by inhalation of aerosolized sterile hypertonic saline solution may be performed if pt is unable to produce sputum - Bronchoscopy with bronchial washings & bronchoalveolar lavage may be performed if necessary
Mycobacterium bacteriology
- Distinguished by their surface lipids, which cause them to be acid-fast bacilli in lab
Active pulmonary TB Tx
- Do not delay treatment if there is a high clinical suspicion
- Multidrug regimen (RIPE includes commonly used first-line drugs)
- Rifampin
- Isoniazid
- Pyrazinamide
- Ethambutol
Miliary TB
- Often called “disseminated TB”
- Due to hematogenous spread & may represent either newly acquired infection or reactivation
- PPD - 50% of untreated cases & sputum smears - in 80%
Transbronchial, liver & BM biopsy + in 2/3
Miliary TB signs and symptoms
- Fever, night sweats, anorexia, weakness & weight loss characterize majority of cases
- Hepatomegaly, splenomegaly, lymphadenopathy, & ocular tubercles may occur
Extrapulmonary TB (rare nowadays because of treatment…however, could occur in HIV/AIDS patients)
- Lymph nodes
- Pleura
- GU tract
- Bones and joints
- Meninges
- Peritoneum
- Any organ system can be affected
HIV transmission
- Anal or vaginal sex
- Sharing needles, syringes, or other drug injection equipment (cookers)
- Babies can also get HIV during pregnancy, birth, or breastfeeding
AIDS (stage 3)
- Defined when CD4 cell count drops below 200 cells/mm or the development of certain opportunistic illnesses
- People with AIDS can have a high viral load and be very infectious
HIV screening guidelines
- U.S. Preventive Services Task Force (USPSTF) upgraded from Grade “C” to Grade “A” recommendation to screen for HIV infection
in adolescents and adults ages 15 to 65, and also < age 15 to > age 65 who are at risk for infection
Diagnosis of HIV
- 4th generation duo antigen/antibody test
- Antibodies take 4 weeks to develop
- P24 antigen and HIV RNA is also tested with 4th generation
- 10 days after exposed, will now become positive
Routine labs in HIV positive patients (general)
- CBC with Diff
- CMP (includes Cr. Glucose and LFTs)
- Lipid Profile
- TB screen (PPD or IGRA)
- Pap smear w/ HPV (cervical and/or anal)
- Gonorrhea and Chlamydia
- Serologies
Serologies used in routine HIV positive patients (general)
- Toxoplasmosis
- Cytomegalovirus
- Varicella IgG
- Hepatitis A/B/C
- RPR
Routine labs in HIV positive patients (HIV specific)
- CD 4 Count
- HIV RNA Assay (viral load)
- HIV-resistance (genotype)
- HLA B*5701 (hypersensitivity to Abacavir )
Medications for initial antiretroviral therapy
- Bicteravir/emtricitabine/tenofovir alafenamide (Biktarvy)
- If B*5701 negative, Dolutegravir/abacavir/lamivudine (Triumeq)
- Dolutegravir (Tivicay) + emtricitabine/tenofovir disoproxil fumarate (Truvada) or emtricitabine/tenofovir alafenamide fumarate (Descovy)
- Raltegravir (Isentress) + emtricitabine/tenofovir disoproxil fumarate (Truvada) or emtrictabine/tenofovir alafenamide fumarate (Descovy)
HIV disease management ART goals
- Keep viral load as low as possible
- Increase CD4 cell count
Prophylaxis is recommended for these diseases
- Varicella-Zoster Virus
- Pneumocystitis Pneumonia (PCP)
- Histoplasmosis (if high risk from occupational exposure ir residence)
- Toxoplasma gondii enceohalitis
- Mycobacterium avium complex (MAC)
Varicella-Zoster Virus prophylaxis
- Any CD4 count
- Recombinant zoster vaccine (Shingrix)
- 2 doses 2 months apart
- Zostavax (zoster vaccine live) is CONTRAINDICATED in AIDS patients (CD4 counts <200)
Pneumocystitis Pneumonia (PCP) prophylaxis
- CD4 < 200
- TMP-SMX (Bactrim) or Dapsone (if sulfa allergy)
Histoplasmosis prophylaxis
- CD4 count < 150
- Iatroconazole
Toxoplasma gondii enceohalitis prophylaxis
- CD4 count < 100
- TMP-SMX (Bactrim) or dapsone (if sulfa allergy)
Mycobacterium avium complex (MAC) prophylaxis
- CD4 count < 50
- Azithromycin or Clarithromycin
Mycobacterium TB latent infection summary
- TST 5mm or greater or positive IGRA, Negative CXR, Negative Symptoms
- Treatment: Isoniazid (INH)* and Rifapentine (RPT) x 3 mo, Rifampin (RIF) x 4 mo, INH and RIF x 3 mo or INH* x 6-9 mo
Mycobacterium TB active disease summary
- TST 5mm or greater** or positive IGRA, positive CXR, positive symptoms (fever, cough, night sweats, weight loss), positive Sputum for Acid Fast Bacilli
- Extrapulmonary symptoms with advanced immunosuppression (nodal involvement, CNS, pleural, pericardial, ascites)
- Treatment: RIPE (plus pyridoxine) or others in CDC guidelines and based on culture and sensitivity report
In TB patients, give pyridoxine (vit B6) if using INH to prevent
- Neuropathy side effect
Pneumocystitis jirovecii
- Ubiquitous fungus
- Most occur in patients unaware of HIV status or low CD 4 counts
Clinical manifestation of Pneumocystitis jirovecii
- Subacute (days to weeks)
- Progressive dyspnea, fever, non-productive cough, and chest discomfort
- +/- hypoxia
- Elevated LDH
- Spontaneous pneumothorax may occur
Pneumocystitis jirovecii CXR
- Diffuse bilateral “ground glass” interstitial infiltrates from the hila in a butterfly pattern or normal
Pneumocystitis hirovecii Tx
- TMP-SMX (Bactrim)
Neurologic syndromes associated with cryptococcosis
- Subacute meningitis
- Meningoencephalitis
Subacute meningitis or meningoencephalitis (cryptococcosis) signs and symptoms
- Fever, malaise, and headache
- Lethargy, altered mental status, photophobia, neck stiffness
- Usually disseminated when diagnosed in HIV patient (skin lesions mimicking molluscum contagiosum, pulmonary infections ARDS mimicking Pneumocystitis…any organ can be involved)
- Ubiquitous in the environment, possible exposure to aged bird droppings may increase risk of infection
Subacute meningitis or meningoencephalitis (cryptococcosis) Dx
- CSF shows mild elevation of protein, low-normal glucose, elevated lymphocytes, increased opening pressures
- Diagnosed with culture, CSF microsocopy, or cryptococcal antigen detection
Subacute meningitis or meningoencephalitis (cryptococcosis) Tx
- Amphotericin B plus flucystosine
Ring enhancing lesions
- Weakness, seizure fast onset (CNS toxoplasmosis…most common in US) – responds quickly to treatment
- Weakness, seizure slow onset (lymphoma)
- Endemic area (TB)
Toxoplasmosis (Toxoplasma gondii)
- Reactivation of latent tissue cysts
- Eating undercooked meat, raw shellfish; exposure to cat litter/feces
Toxoplasmosis (Toxoplasma gondii) clinical manifestations
- Focal encephalitis (headache, confusion, motor weakness, fever) or non-specific headache and psychiatric symptoms
Toxoplasmosis (Toxoplasma gondii) Tx
- Pyrimethamine plus sulfadiazine (clindamycin in sulfa allergy) plus leucovorin
Progressive Multifocal Leukoencephalopathy (PML)
- Major opportunistic infection causing reactivation of the John Cunningham (JC) virus
- May occur shortly after initiation of ART due to immune reconstitution inflammatory syndrome (IRIS)
Progressive Multifocal Leukoencephalopathy (PML) clinical manifestations
- Altered mental status
- Visual changes
- Ataxia
- Seizures
Progressive Multifocal Leukoencephalopathy (PML) imaging
- Multifocal process limited to the white matter
Progressive Multifocal Leukoencephalopathy (PML) Dx
- Brain biopsy
Progressive Multifocal Leukoencephalopathy (PML) Tx
- ART to restore immune system
- Adding high dose glucocorticoids if evidence of brain swelling due to immune response inflammatory syndrome (IRIS)
Progressive Multifocal Leukoencephalopathy (PML) prognosis
- Often fatal
CMV retinitis
- Most common clinical manifestation of CMV in HIV patients
- Usually starts as unilateral, but can progress to bilateral if not treated
CMV retinitis presentation
- May be asymptomatic or present with floaters, scotomata, or peripheral visual field defects
- Full-thickness necrotizing retinitis, with classic “fluffy yellow-white” retinal lesions with or without intraretinal hemorrhage
CMV retinitis Tx
- IV ganciclovir followed by oral valganciclovir
Other HIV presentations
- CMV polyradiculoapthy (saddle paresthesias, asymmetiric lower extremity weakness, bowel dysfunction)
- Emergency…diagnosed via CMV culture of CSF and TX
Shingles in young pt (25% chance this is HIV) Tx
- Antivirals & pain meds
- Acyclovir, valacyclovir, or famciclovir
- Hospitalization with IV acyclovir if disseminated
- Emergent ophthalmic referral if involving trigeminal (V1)
Kaposi’s sarcoma
- Human Herpes Virus 8
- Transmission most likely via oral (kissing)
- Red-Purple papular lesions and plaques, nodules with edema (similar to Bacillary Angiomatosis)
Kaposi’s sarcoma Tx
- TX with ART, others may need low dose chemotherapy
Risk of transmission from a single percutaneous needle stick or cut with a scalpel from an infected patient
- Hepatitis B is about 6-30%
- Hepatitis C is about 1.8%
- HIV is about 0.3%
Factors that increase the riskof exposure to body fluids
- Failure to adopt universal precautions
- Not following established a protocol of safety
- Performing high-risk procedures that increase the risk of blood exposure
- Using needles and other sharp devices that lack safety features
What should be the first response to a percutaneous exposure?
- Wash the area thoroughly with soap and water
- Punctures and small lacerations could be cleaned with alcohol based hand solution
- Mucous membranes should be extensively irrigated with water or saline
Second response to percutaneous exposure (after cleaning)
- Report the exposure and obtain Hepatitis and HIV screening for both the provider and the source patient (per protocol of institution) and discuss need for post-exposure prophylaxis
What are the indications for HIV Post Exposure Prophylaxis (PEP)?
- A percutaneous, mucous membrane, or nonintact skin exposure to blood or bloody body fluids of a patient with known HIV infection
- If HIV status of the source patient is unknown & if the source has risk factors for HIV infection (injection drug users, men who have sex with men) or symptoms suggesting HIV infection & you are waiting for HIV testing
When should HIV PEP start?
- As soon as possible! Less than 2 hours after exposure give a “starter pack” (don’t wait for HIV results if they are not back yet!)
- If more than 72 hours, most should not get PEP
- If it is a very high-risk exposure (sharps injuries from a needle that was in an artery or vein of an HIV-infected source patient), PEP can be offered up to one week after the exposure
What PEP meds should be used (3-drug regimen)?
- tenofovir DF 300 mg and fixed dose combination
- emtricitabine 200 mg (Truvada) once daily
with
- raltegravir (Isentress) 400 mg twice daily
or
dolutegravir (Tivicay) 50 mg once daily
How long should PEP be taken?
- 4 weeks
Discontinue if source patient is shown to be negative
Hepatitis B prophylaxis if the healthcare provider is already vaccinated and patient is HBsAg positive
- Check an anti-HBs level in the healthcare worker
- If the post-vaccination anti-HBs level is high (greater than 10 mIU/mL), this is known to beprotective, and there is no need for further treatment, and a booster shot is not recommended
- If the post-vaccination anti-HBs titer is low, the healthcare worker should be administered hepatitis B immunoglobulin
Hepatitis B prophylaxis if the healthcare provider is already vaccinated and patient is HBsAg negative
- Observe the healthcare worker and monitor anti-HBs levels
Hepatitis B prophylaxis if the healthcare provider is already vaccinated if patient has been discharged or not available for testing
- Most infectious disease experts treat such cases as if the source was HBsAg negative unless the source has a high risk for HBV infection (such as current or former IV drug use)
- In this case, the assumption is made that the patient is HBsAg positive, and Post-exposure prophylaxis is initiated
Hepatitis B prophylaxis if the healthcare provider is NOT vaccinated and patient is HBsAg positive
- The healthcare worker should be administered HBV immunoglobulin immediately, followed by a rapid course of active immunization starting 14 days later
Hepatitis B prophylaxis if the healthcare provider is NOT vaccinated and patient is HBsAg negative
- No need to administer hepatitis B immunoglobulin
- Healthcare worker should strongly be recommended to get the Hepatitis B vaccine
Hepatitis B prophylaxis if the healthcare provider is NOT vaccinated and patient is not available for testing
- If there is any suspicion about the patient’s clinical status, workers must be offered Hepatitis B immunoglobulin, and active vaccination should be recommended in 14 days time
